AB0415 UPADACITINIB. EFFECTIVENESS AND SAFETY IN PATIENTS WITH REFRACTORY RHEUMATOID ARTHRITIS
Authors: N. Roldan Ruiz, C. Ramos Giráldez, C. Azabal Perez, R. Martínez, M. L. Velloso Feijoo, J. L. Marenco
Journal: Annals of the Rheumatic Diseases (2022)

Background Upadacitinib is the third janus kinase (JAKi) inhibitor approved for rheumatoid arthritis after baricitinib and tofacitinib. Upadacitinib is a selective JAK1 inhibitor, and is indicated for the treatment of moderate to severe active RA in adult patients with inadequate response or intolerance to one or more DMARDs. Objectives To describe the effectiveness and safety data of upadacitinib in patients with moderate-severe RA refractory to multiple synthetic and/or biologic DMARDs. Methods Descriptive and retrospective observational study conducted in patients who met RA classification criteria, refractory to synthetic and/or biologic DMARDs in the Rheumatology department of the Valme Hospital. Epidemiological, clinical, analytical, and safety and treatment-related variables were collected. A descriptive quantitative analysis of the data was performed. Results Forty five patients were included (37 women and 8 men), with a mean age of 53 years and mean time of RA evolution of 11 years. Of the patients, 44.4% had some cardiovascular risk factor. With respect to previous treatment, 100% were on DMARDsc, with a median of 2 DMARDsc per patient. Regarding biologic or targeted therapy, 77.8% had a history of biologic therapy failure with a median of 1 biologic; in addition, 8 patients had received at least 3 previous biologic drugs prior to upadacitinib. A total of 28.9% (13 patients) had previously received JAKi, discontinued due to secondary failure or from clinical trials at other centers. In terms of disease activity at the start of upadacitinib, patients had a mean of number of swollen joints (SJC) 3, number of tender joints (TJC) 4, CRP 11 mg/dl, DAS28 of 4.23 and CDAI of 21.5. When starting upadacitinib, 80% of the patients were on steroid therapy, 51% with doses &gt; 5 mgr/day of prednisone. Combination therapy with DMARDs was maintained in 76.3% of patients (56.7% MTX, 36.7% LFN and the rest with SSZ). The results were analyzed after a median of 7 months from the start of upadacitinib: DMARDsc were discontinued in 4 patients and the steroid dose was reduced in 58.3% of the total, being discontinued in 21.2%. With respect to disease activity analyzed post-treatment in patients who maintained the drug, a mean of SJC 0, TJC 2, CRP 0.8 mg/dl, DAS28 2.7 and CDAI 12.5 were observed (Table 1). The drug was discontinued in 11 patients: 5 for adverse events (headache, hypersensitivity, gastrointestinal discomfort, instability accompanied by photopsia, lymphopenia and irritative cough) that resolved after drug discontinuation, 5 for primary failure and 1 for secondary failure. No cases of herpes, thrombosis or cardiovascular events were recorded. Table 1. Medians pre-treatment and post-treatment outcomes in patients who maintained upadacitinib: SJC, TJC, C-Reactive Protein (CRP) and disease activity indices DAS28 and CDAI. Pre upadacitinib Post-treatment (medians 7 months) Statistical significance SJC 3 0 &lt; 0,05 TJC 4 2 0,03 CRP 11 0,8 &lt; 0,05 DAS28 4,23 2,7 &lt; 0,05 CDAI 21,5 12,5 &lt; 0,05 Conclusion Upadacitinib managed to control disease activity in a high percentage of our series of patients resistant to multiple synthetic and/or biologic DMARDs, making it possible to reduce or even suspend steroid treatment in a significant number of patients, so it may be an option to consider in patients with refractory RA. Longer-term studies are needed to continue evaluating the effectiveness, safety and survival of the drug in real clinical practice. References [1]Strand V, Schiff M, Tundia N, Friedman A, Meerwein S, Pangan A, Ganguli A, Fuldeore M, Song Y, Pope J. Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs. Arthritis Res Ther. 2019 Dec 2;21(1):263. Disclosure of Interests None declared